scholarly journals Immune-Regulatory and Molecular Effects of Antidepressants on the Inflamed Human Keratinocyte HaCaT Cell Line

2021 ◽  
Author(s):  
Curzytek K. ◽  
Maes M. ◽  
Kubera M.
Keyword(s):  
Cell Line ◽  
Inflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Hacat Cell ◽  
Antidepressant Drugs ◽  
Skin Inflammation ◽  
Hacat Cell Line ◽  
Tnf Α ◽  
Ifn Γ ◽  
Pro Inflammatory Cytokines

AbstractAllergic contact dermatitis (ACD) is a T cell-mediated type of skin inflammation resulting from contact hypersensitivity (CHS) to antigens. There is strong comorbidity between ACD and major depression. Keratinocytes release immunomodulatory mediators including pro-inflammatory cytokines and chemokines, which modulate skin inflammation and are crucial cell type for the development of CHS. Our previous studies showed that fluoxetine and desipramine were effective in suppressing CHS in different mouse strains. However, the immune and molecular mechanisms underlying this effect remain to be explored. The aim of the current study was to determine the immune and molecular mechanisms of action of antidepressant drugs engaged in the inhibition of CHS response in the stimulated keratinocyte HaCaT cell line. The results show that LPS, TNF-α/IFN-γ, and DNFB stimulate HaCaT cells to produce large amounts of pro-inflammatory factors including IL-1β, IL-6, CCL2, and CXCL8. HaCaT stimulation was associated with increased expression of ICAM-1, a cell adhesion molecule, and decreased expression of E-cadherin. Imipramine, desipramine, and fluoxetine suppress the production of IL-1β, CCL2, as well as the expression of ICAM-1. LPS and TNF-α/IFN-γ activate p-38 kinase, but antidepressants do not regulate this pathway. LPS decreases E-cadherin protein expression and fluoxetine normalizes these effects. In summary, the antidepressant drugs examined in this study attenuate the stimulated secretion of pro-inflammatory cytokines, chemokines, and modulate adhesion molecule expression by the HaCaT cell line. Therefore, antidepressants may have some clinical efficacy in patients with ACD and patients with comorbid depression and contact allergy.

scholarly journals Anti-Inflammatory Activity of a Medicinal Herb Extract Mixture, HM-V, on an Animal Model of DNCB-Induced Chronic Skin Inflammation

Plants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1546
Author(s):  
Sungbae Park ◽  
Sangmin Lee ◽  
Youngho Weon ◽  
Taewook Kim ◽  
Hakwon Kim ◽  
...  
Keyword(s):  
Animal Model ◽  
Inflammatory Cytokines ◽  
Skin Diseases ◽  
Skin Inflammation ◽  
Medicinal Herb ◽  
Inflammatory Skin Diseases ◽  
Tnf Α ◽  
Ifn Γ ◽  
Chronic Skin ◽  
Pro Inflammatory Cytokines

Chronic inflammatory skin diseases, such as atopic dermatitis, are caused by the accumulation of immune cells and the overproduction of chemokines, including CCL17 and CCL22, due to the activation of pro-inflammatory cytokines secreted from keratinocytes. In the present study, the inhibitory activity of HM-V on tumor necrosis factor alpha (TNF-α)/interferon gamma (IFN-γ)-induced pro-inflammatory cytokines was examined in human keratinocytes (HaCaTs) and 2,4-dinitrofluorobenzene (DNCB)-induced chronic skin contact dermatitis animal models. Traditional Asian medicinal herb extracts mixture (HM-V), which have been extensively used in Asian medicine, were utilized. In TNF-α/IFN-γ-induced HaCaTs, HM-V strongly inhibited mRNA and protein expression of CCL17 and CCL22 in a concentration-dependent manner. The expression of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 was also inhibited. Therefore, localized administration of HM-V in the DNCB-induced animal model alleviated immune cell deposition and skin inflammation. The results indicate that HM-V exerts inhibitory effects on keratinocyte production of CCL17 and CCL22. Furthermore, HM-V may be a useful anti-inflammatory agent for the prevention and treatment of inflammatory skin diseases.

IL-4, BUT NOT IL-13, MODULATES TARC (THYMUS AND ACTIVATION-REGULATED CHEMOKINE)/CCL17 AND IP-10 (INTERFERON-INDUCED PROTEIN OF 10kDa)/CXCL10 RELEASE BY TNF-α AND IFN-γ IN HaCaT CELL LINE

Cytokine ◽  
2002 ◽  
Vol 20 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Takashi Kakinuma ◽  
Koichiro Nakamura ◽  
Motoshi Wakugawa ◽  
Shoichiro Yano ◽  
Hidehisa Saeki ◽  
...  
Keyword(s):  
Cell Line ◽  
Hacat Cell ◽  
Hacat Cell Line ◽  
Tnf Α ◽  
Ifn Γ

scholarly journals Modulation of ACE-2 mRNA by inflammatory cytokines in human thyroid cells: a pilot study

Endocrine ◽  
2021 ◽  
Author(s):  
Francesca Coperchini ◽  
Gianluca Ricci ◽  
Laura Croce ◽  
Marco Denegri ◽  
Rubina Ruggiero ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Combination Treatment ◽  
Primary Cultures ◽  
Human Thyroid ◽  
Thyroid Cell ◽  
Mrna Levels ◽  
Thyroid Cells ◽  
Tnf Α ◽  
Ifn Γ ◽  
Pro Inflammatory Cytokines

Abstract Introduction Angiotensin-converting-enzyme-2 (ACE-2) was demonstrated to be the receptor for cellular entry of SARS-CoV-2. ACE-2 mRNA was identified in several human tissues and recently also in thyroid cells in vitro. Purpose Aim of the present study was to investigate the effect of pro-inflammatory cytokines on the ACE-2 mRNA levels in human thyroid cells in primary cultures. Methods Primary thyroid cell cultures were treated with IFN-γ and TNF-α alone or in combination for 24 h. ACE-2 mRNA levels were measured by RT-PCR. As a control, the levels of IFN-γ inducible chemokine (CXCL10) were measured in the respective cell culture supernatants. Results The mean levels of ACE-2 mRNA increased after treatment with IFN-γ and TNF-α in all the thyroid cell preparations, while the combination treatment did not consistently synergically increase ACE-2-mRNA. At difference, CXCL10 was consistently increased by IFN-γ and synergically further increased by the combination treatment with IFN-γ + TNF-α, with respect to IFN-γ alone. Conclusions The results of the present study show that IFN-γ and, to a lesser extent TNF-α consistently increase ACE-2 mRNA levels in NHT primary cultures. More interestingly, the combined stimulation (proven to be effective according to the synergic effect registered for CXCL10) produces different responses in terms of ACE-2 mRNA modulation. These results would suggest that elevated levels of pro-inflammatory cytokines could facilitate the entering of the virus in cells by further increasing ACE-2 expression and/or account for the different degree of severity of SARS-COV-2 infection. This hypothesis deserves to be confirmed by further specific studies.

scholarly journals Plasma cytokine response in mice with bacterial infection

2000 ◽  
Vol 9 (5) ◽  
pp. 229-234 ◽  
Author(s):  
Maja Abram ◽  
Darinka Vučković ◽  
Branka Wraber ◽  
Miljenko Doric
Keyword(s):  
Bacterial Infection ◽  
Inflammatory Cytokines ◽  
Plasma Levels ◽  
Clinical Status ◽  
Blood Levels ◽  
Large Individual ◽  
Bacterial Number ◽  
Tnf Α ◽  
Ifn Γ ◽  
Pro Inflammatory Cytokines

Background:Exposure to microorganisms elicts the production of cytokines. These soluble factors enhance several innate immune functions and regulate the ensuing specific immune response aimed at limiting the spread of infection.Aim:This study was undertaken to quantify the plasma levels of pro-inflammatory cytokines during the course of primaryListeria monocytogenesandCampylobacter jejuniinfection. Using anin vivoinfection the relationship between endogenous cytokines and the bacterial number in the liver of infected animals was examined.Methods:C57BL/6 mice were infected by the intraperitoneal route. At different time points we determined the number of colony-forming units of bacteria in the liver of infected animals and paralled these with the plasma levels of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) measured by enzyme immunoassays.Results:L. monocytogenes infection lasted 10–11 days. IFN-γ production occurred in the early phase but was more pronounced after day 4, following the appearance of specific immunity. The duration of experimental campylobacteriosis was 15 days. Early IFN-γ production was not significant but a progressive rise of this cytokine in plasma was seen during the second week post infection. Mice produced measurable amounts of plasma TNF-α immediately after being given viableL. monocytogenes, peaking on day 2–3 when the greatest number of bacteria was present in the examined organs. DuringC. jejuniinfection plasma TNF-α was produced in a similar manner, but the highest concentrations were found a few days later than in listeriosis, in correlation with the different course of campylobacteriosis. The quantity of IL-6 increased and decreased in concordance with clearance ofL. monocytogenesand the clinical status of the animals.C. jejunidid not promote the induction of this cytokine. This is to some extent an unusual finding. With respect to the role of IL-6 in Th2 responses and antibody production, the appearance of this cytokine in campylobacteriosis was more expected.Discussion:During systemic bacterial infection, a network of pro-inflammatory cytokines is activated and blood levels of these cytokines are elevated, albeit inconsistently, with large individual variations and depending on microbial characteristics and structure.

scholarly journals The effect of hemantane on the level of pro-inflammatory cytokines in the nigrocaudate complex of the brain of mice with experimental parkinsonism

2021 ◽  
pp. 45-49
Author(s):  
Н.А. Воронина ◽  
В.Г. Кучеряну ◽  
Л.А. Ветрилэ ◽  
В.В. Голоборщева ◽  
И.Г. Капица ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Clinical Stage ◽  
Late Phase ◽  
Brain Structures ◽  
Interferon Γ ◽  
Nigrostriatal System ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tnf Α ◽  
Ifn Γ ◽  
Pro Inflammatory Cytokines

Целью данных исследований явилось изучение влияния гимантана (N-(2-адамантил)-гексаметиленимина гидрохлорида) на уровень провоспалительных цитокинов IL-1β, IL-6, интерферона-γ (ИФН-γ) и фактора некроза опухоли-α (ФНО-α) в нигрокаудатном комплексе мышей на ранней и поздней клинической фазе экспериментального паркинсонического синдрома (ПС), для выяснения его антипаркинсонического эффекта. Методы исследования: Раннюю и позднюю клиническую фазу ПС создавали у мышей линии C57BL/6J внутрибрюшинным введением пронейротоксина 1-метил-4-фенил-1,2,3,6-тетрагидропиридина (МФТП) в дозах 12 мг/кг или 20 мг/кг по 4 инъекции с интервалом 2 часа, соответственно. Гимантан вводили мышам внутрибрюшинным в дозе 20 мг/кг, предварительно каждый раз за 30 мин до введения МФТП. Содержание цитокинов в структурах мозга мышей определяли методом иммуноферментного анализа с использованием тест-систем производства «Cloud-Clone Corporation», США и считывающего устройства «ИФА-reader» прибора «ImmunoChem-2100», США. Результаты: Показано, что уровень IL-1β, IL-6, ИФН-γ и ФНО-α в нигрокаудатном комплексе мозга мышей возрастает как на ранней, так и на поздней фазах развития ПС. Предварительное применение гимантана снижало в нигрокаудатном комплексе мышей содержание цитокинов IL-1β, ИФН-γ и ФНО-α на ранней фазе, и только одного из 4 изученных (IL-6) - на поздней фазе развития ПС. Предполагается, что антипаркинсонический эффект гимантана на ранней клинической стадии МФТП-индуцированного ПС осуществляется, в том числе, за счёт снижения уровня провоспалительных цитокинов в нигростриатной системе, предупреждая снижение жизнеспособности дофаминергических нейронов. The aim of this work was to study the effect of Hemantane (N-(2-adamantyl)-hexamethyleneimine hydrochloride) on the level of pro-inflammatory cytokines IL-1β, IL-6, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) in the nigrocaudate complex of mice in early and late clinical phases of experimental Parkinsonian syndrome (PS) to elucidate its antiparkinsonian effect. Material and methods: The early and late clinical phases of PS were created in C57BL / 6J mice by 4 intraperitoneal injections at 2-h intervals of a proneurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), at a dose of 12 mg/kg or 20 mg/kg. Hemantane was injected intraperitoneally at a dose of 20 mg/kg 30 min before each MPTP administration. Concentrations of cytokines in mouse brain structures were measured by enzyme-linked immunosorbent assay (ELISA) using Cloud-Clone Corporation (USA) test systems and an ImmunoChem-2100 (USA) ELISA reader. Results: Concentrations of IL-1β, IL-6, IFN-γ, and TNF-α in the nigrocaudate complex were increased both in the early and late phases of PS. Prior administration of hemantane reduced the content of IL-1β, IFN-γ, and TNF-α in the nigrocaudate complex at the early phase and the content of only one of the 4 studied cytokines (IL-6) at the late phase of PS. It was assumed that the antiparkinsonian effect of hemantane at the early clinical stage of MPTP-induced PS involves a decrease in proinflammatory cytokines in the nigrostriatal system, which prevents the impairment of the viability of dopaminergic neurons.

scholarly journals Maternal Serum Levels of Interferon-gamma, Tumor Necrotic Factor-alpha and Progesterone of Infertile Women on In vitro Fertilization before and after Treatment

2020 ◽  
pp. 38-44
Author(s):  
N. Osakue ◽  
C. C. Onyenekwe ◽  
F. A. Ehiaghe ◽  
J. E. Ahaneku ◽  
J. I. Ikechebelu ◽  
...  
Keyword(s):  
In Vitro Fertilization ◽  
Inflammatory Cytokines ◽  
First Trimester ◽  
Vitro Fertilization ◽  
Tnf Α ◽  
Before And After ◽  
First Trimester Of Pregnancy ◽  
Ifn Γ ◽  
Pro Inflammatory Cytokines

Background: In vitro fertilization (IVF) is an assisted reproductive technology (ART) that is widely used globally in the treatment of infertility. Infertility can occur due to male factors, female factors or both. Aim: This is the first Nigerian study that sets out to observe the levels and relationship between circulating pro-inflammatory cytokines (IFN-γ, TNF-α) and progesterone (PG) in Nigerian women undergoing in vitro fertilization pre and post treatment and their possible effect on pregnancy outcome. Materials and Methods: This observational study randomly selected sixty-two (62) infertile females below 45 year of age who enrolled in the IVF treatment at Lily Hospitals, Warri and Shepherd Specialist Hospital, Warri, Southern Nigeria. Only data of the thirteen (13) infertile females who became pregnant after the IVF treatment where followed up and presented in this study. Five (5) ml of whole blood were collected into plain tubes on day 3 of the menstrual cycle of all the participants from the ante-cubital vein before and after IVF procedure using standard laboratory collection technique. Ovarian stimulation was done using the long gonadotropin-releasing hormone agonist protocol. Oocyte retrieval transfer was done using ultrasound-guided fine-needle aspiration and embryo transfer was done using ultrasound-guided embryo transfer. IFN-γ, TNF-α and PG were estimated using enzyme-linked immunosorbent assay method. Results and Conclusion: Significant increase in the levels of TNF-α and PG at the second trimester and third trimester of pregnancy when compared with the first trimester of pregnancy (p = 0.000). While the level of IFN-γ was significantly increased in the second trimester of pregnancy when compared with the first trimester of pregnancy (p = 0.000). It is evident from the study that both pro-inflammatory cytokines (IFN-γ and TNF-α) act in synergy to maintain the level of progesterone which act as an anti-inflammatory agent to regulate the activities of the pro-inflammatory cytokines for successful oocytes implantation and maturation.

scholarly journals Dysbiotic Gut Microbiota and Dysregulation of Cytokine Profile in Children and Teens With Autism Spectrum Disorder

2021 ◽  
Vol 15 ◽  
Author(s):  
Xia Cao ◽  
Kevin Liu ◽  
Jun Liu ◽  
Yen-Wenn Liu ◽  
Li Xu ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Inflammatory Cytokines ◽  
Gut Microbiome ◽  
Plasma Levels ◽  
Autism Spectrum ◽  
Tnf Α ◽  
Healthy Control ◽  
Ifn Γ ◽  
The Relationship ◽  
Pro Inflammatory Cytokines

Inflammation and the gut-brain axis have been implicated in the pathogenesis of autism spectrum disorders (ASDs). To further understand the relationship between aberrant immune responses and dysbiotic features of the gut microbiome in ASD, we enrolled 45 ASD individuals and 41 healthy control subjects with ages ranging from 2 to 19 years. We found that ASD group subjects have significantly higher plasma levels of IL-2, IL-4, IL-5, IL-6, IL-10, TNF-α, TNF-β, and IFN-γ when compared to healthy controls (FDR-adjusted p < 0.05). The plasma levels of pro-inflammatory cytokines IFN-γ and IL-6 are found to be further associated with several largely pathogenic gut microbiota uniquely detected in subjects with ASD. Furthermore, the ASD gut microbiome is characterized by reduced levels of several beneficial microbiota, including Bacteroides (FDR-adjusted p < 0.01) and Lachnospiraceae (FDR-adjusted p < 0.001). Analysis of Lachnospiraceae family and genus level taxa suggested that relative abundances of such taxa are negatively correlated with pro-inflammatory signaling cytokines IFN-γ and IL-6, particularly in subjects with severe ASD as defined by CARS (p < 0.05). Several largely pathogenic genera are determined to be associated with the pro-inflammatory cytokines IFN-γ and IL-6 (FDR-adjusted p < 0.1). Additionally, IL-4 is significantly negatively correlated with CARS total score (p < 0.05). Based on such results, we propose that the association between the disturbances of specific cytokines and alterations in gut microbiota abundance observed in children and adolescents with ASD provides additional evidence on the induction of aberrant pro-inflammatory mechanisms in ASD and its early diagnosis.

A phase I study of mRNA-2752, a lipid nanoparticle encapsulating mRNAs encoding human OX40L, IL-23, and IL-36γ, for intratumoral (iTu) injection alone and in combination with durvalumab.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3092-3092
Author(s):  
Manish R. Patel ◽  
Todd Michael Bauer ◽  
Antonio Jimeno ◽  
Ding Wang ◽  
Patricia LoRusso ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Solid Tumor ◽  
Human Study ◽  
Post Treatment ◽  
Tumor Shrinkage ◽  
Tumor Patients ◽  
Combination Methods ◽  
Tnf Α ◽  
Ifn Γ ◽  
Pro Inflammatory Cytokines

3092 Background: mRNA-2752 is a novel mRNA-based therapeutic agent encoding OX40L T cell co-stimulator, IL-23 and IL-36γ pro-inflammatory cytokines. Here we present findings from a first-in-human study of iTu mRNA-2752 in solid tumor patients as monotherapy or in combination with durvalumab (durva). At the time of presentation, data will encompass the monotherapy escalation MTD/RDE along with the supporting translational work, and the available data in combination. Methods: iTu mRNA-2752 was administered every 2 weeks for up to 7 doses as monotherapy or in combination with durva in patients with advanced solid malignancy or lymphoma. Biomarker analyses include measurement of IL-23, IL-36γ and pro-inflammatory cytokine proteins in pre- and post-treatment tumor biopsies and plasma. PD-L1 immunohistochemistry was used to further characterize baseline status and changes to the TME with treatment. Results: As of 20 December 2019, 23 solid tumor patients have been treated either with mRNA-2752 alone (n = 14) or in combination (n = 9) and has been well tolerated with no dose limiting toxicities or related grade 3/4 toxicities. Of the 17 patients evaluated per RECIST and iRECIST, 1 had a PR (iRECIST), 6 had SD, and 10 had PD. The patient with a PR (52% tumor reduction) received 0.5 mg mRNA-2752 with durva, and had aPD-1/L1 naïve squamous-cell bladder carcinoma. Tumor shrinkage was observed in an additional 5 patients in injected and/or uninjected lesions in both monotherapy and combination. Preliminary biomarker data showed increased IL-23 and IL-36γ protein expression after 6-24 hours, and increased levels of downstream cytokines IL-22 and IL-6, respectively. Pro-inflammatory cytokines (e.g. IFN-γ, TNF-α) were also significantly increased at 1 day and 1-week post-treatment. Significant increases in PD-L1 expression predominantly in tumor-associated immune cells were observed after first dose and persisted up to 29 days after treatment. Conclusions: iTu mRNA-2752 given as monotherapy and in combination with durva is tolerable at all dose levels studied, and administration can be associated with tumor shrinkage. Analyses of tumor and plasma biomarkers suggest a sustained immunomodulatory effect of treatment that includes elevated IFN-γ, TNF-α, and PD-L1 levels. These data support the ongoing testing of the mRNA-2752/durva combination in the dose escalation part of the study. Clinical trial information: NCT03739931 .

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